Phase III Randomized International Open Label Clinical Trial of Treatment Intensification With Docetaxel Plus Apalutamide in Patients With Metastatic Hormone-sensitive Prostate Cancer Who Did Not Achieve a Deep PSA Response After Initial Treatment With Apalutamide: REINFORCE Trial.
This is a phase III, randomized, open-label, multi-center study to assess the efficacy of treatment intensification with docetaxel plus apalutamide and ADT, assessed by event-free survival, in patients with mHSPC who do not achieve deep PSA response (≤0,2 ng/ml or PSA90 response in combination with a PSA ≤ 4 ng/ml) after initial treatment with apalutamide and ADT. A non-deep PSA response is defined as PSA \> 0.2 ng/ml in combination with a PSA response \< 90%, or a PSA response ≥90% in combination with a PSA \> 4 ng/ml.
• Written informed consent. Each patient must sign an informed consent form (ICF) indicating that he understands the purpose of and procedures, required for the study, and is willing to participate in the study.
• Patient must be a man ≥18 years of age.
• Histologically or cytologically confirmed adenocarcinoma of prostate.
• Metastatic hormone-sensitive prostate cancer.
• PSA \>5 ng/ml at diagnosis of metastatic disease.
• Patients eligible to continue treatment with apalutamide and ADT and without contra-indication to receive docetaxel.
• Patients with at least 24 weeks and no more than 30 weeks of apalutamide.
• Patients with a maximum of 12 weeks ADT before apalutamide initiation.
• Lack of achievement of deep PSA response after 24 weeks and no more than 30 weeks of apalutamide. Deep PSA response is defined as PSA ≤ 0.2 ng/ml or PSA response ≥ 90% in combination with a PSA ≤4 ng/ml. Therefore, a non-deep PSA response is defined as PSA \> 0.2 ng/ml in combination with a PSA response \< 90%, or a PSA response ≥90% in combination with a PSA \> 4 ng/ml.
⁃ Patients who have not progressed to apalutamide.
⁃ Patients that are tolerating adequately apalutamide 240 mg daily and with no toxicity higher than G1 at inclusion.
⁃ Be able to swallow whole apalutamide film-coated tablets.
⁃ Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
⁃ Clinical laboratory values at screening:
∙ hemoglobin ≥10.0 g/dL,
‣ absolute neutrophil count ≥1.5 × 10\*9/L,
‣ platelet count ≥100 × 109/L, The patient must not have received any growth factor within 4 weeks or a blood transfusion within 7 days of the hematology laboratory sample obtained at screening
‣ serum alanine aminotransferase and/or aspartate transaminase ≤1.5 × the upper limit of normal (ULN),
‣ total bilirubin ≤ ULN,
‣ creatinine ≤2.0 × ULN
⁃ Sexually active men must agree to use an external condom as an effective barrier method and refrain from sperm donation, and their female partners of childbearing potential must practice a highly effective method of contraception during and for 3 months after treatment with apalutamide and for 6 months after treatment with docetaxel.